V-RAS GENES FROM HARVEY AND BALB MURINE SARCOMA-VIRUSES CAN ACT AS INITIATORS OF 2-STAGE MOUSE SKIN CARCINOGENESIS
V-RAS GENES FROM HARVEY AND BALB MURINE SARCOMA-VIRUSES CAN ACT AS INITIATORS OF 2-STAGE MOUSE SKIN CARCINOGENESIS
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DOI：
10.1016/0092-8674(86)90665-3
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发表时间：
1986-08-01
期刊：
影响因子：
64.5
通讯作者：
BALMAIN, A
中科院分区：
文献类型：
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作者：
BROWN, K;QUINTANILLA, M;BALMAIN, A
通过将逆转录病毒直接应用于小鼠皮肤，将激活的Harvey小鼠肉瘤病毒ras基因引入体内表皮细胞。随后用肿瘤促进剂12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）治疗诱导良性乳头状瘤，其中一些进展为浸润性癌。用病毒启动至少4个月是不可逆的，因为TPA治疗在此潜伏期后4周内产生乳头状瘤。病毒整合位点的分析表明，癌是克隆起源。乳头状瘤和癌都表达病毒特异性ras mRNA和病毒形式的ras P21蛋白。结果表明，激活的ras基因可替代化学致癌物启动小鼠皮肤癌的发生。该系统提出了一种新的方法，在上皮肿瘤发生的癌基因的生物学作用的体内分析。
Activated Harvey murine sarcoma virus ras genes were introduced into epidermal cells in vivo by direct application of retroviruses to mouse skin. Subsequent treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced benign papillomas, some of which progressed to invasive carcinomas. Initiation with virus was irreversible for at least 4 months, since TPA treatment after this latency period produced papillomas within 4 weeks. Analysis of viral integration sites showed that carcinomas are clonal in origin. Both papillomas and carcinomas express virus-specific ras mRNA and the viral form of ras P21 protein. The results show that activated ras genes can replace chemical carcinogen in initiation of mouse skin carcinogenesis. This system presents a novel approach to in vivo analysis of the biological role of oncogenes in epithelial tumorigenesis.